The Two-Mile Square Reservation was a land division in the Northwest Territory.

As the Northwest Territory was organized in the late 1700s, the federal government sold large portions of land to private companies and individuals. The purchasers included the Ohio Company of Associates, the Scioto Company, land speculator John Cleves Symmes, and numerous other businesses and people. Individual states, including Connecticut and Virginia, also held claims in the territory. The United States government held the remaining land and slowly sold it. Some of the money paid off debts left over from the American Revolution. American Indians occupied much of these lands during the early years of settlement, but they were gradually forced out as more white settlers moved into Ohio.

Ohio lands were surveyed and sold by the federal government, private individuals, and by the states of Virginia and Connecticut. Since parts of the state were surveyed at different times, Ohio was divided into areas called survey "districts" or "land grants." Among these districts was the Two-Mile Square Reservation. The United States government formally acquired this territory in the Treaty of Greenville. Under this treaty, the Northwest Territory's native population received most of the land in modern-day northwestern Ohio, but they were forced to relinquish several small parcels, including the Two-Mile Square Reservation, to the United States government. This particular parcel was located on the Sandusky River and included the lower falls on the river, which made the waterway impassable by boat. It remains unclear why the United States government desired this land, but one possible explanation is that federal officials intended to use this site to distribute goods to American Indians as required under the Treaty of Greenville.